Combinatorial arrays of materials are useful, e.g., in screening compositions for unique or improved characteristics. In the biosciences, combinatorial arrays can be useful in discovery of molecules with desirable binding or catalytic activities. In materials sciences, combinatorial arrays have been constructed to discover materials with useful physical, catalytic, chemical, mechanical, or optical characteristics. Combinatorial technologies can provide efficient ways to create and screen materials useful in medicine, electronics, optics, packaging, machinery, and more.
Arrays can be found in many fields, for example: printing, mathematics, video display, art, life sciences, electronics, and the like. These arrays typically include many elements with common characteristics grouped in homogenous zones of the array to form interesting or useful patterns (such as, images, textures, or environments). Combinatorial arrays typically include substrates with randomly or systematically different constituents combined at different locations. Large scale combinatorial libraries can include extensive arrays of different materials combinations at different locations providing screenable populations containing variety of useful properties.
Combinatorial arrays in chemistry have been found useful in discovery of chemicals with unique properties or in finding improved versions of previously known molecules. In U.S. Pat. No. 5,463,564, System and Method of Automatically Generating Chemical Compounds with Desired Properties, to Agrafiotis, et al., a computer based, iterative process generates chemical entities with defined chemical properties. During each iteration of the process, a directed diversity chemical library is robotically generated in accordance with robotic synthesis instructions; the compounds in the directed diversity chemical library are analyzed to identify compounds with the desired properties; structure-property data are used to select compounds to be synthesized in the next iteration; and new robotic synthesis instructions are automatically generated to control the synthesis of the directed diversity chemical library for the next iteration. The combinatorial organic chemistries of Agrafiotis, et al., are carried out, e.g., by combinatorial robots that mix and split bead substrates to different organic reagents or robots that sequentially transfer reagents to solid support array locations.
Combinatorial arrays in biology can include random or systematic arrays of biomolecules on substrates, such as beads or grids on solid supports. In U.S. Pat. No. 5,424,186, Very Large Scale Immobilized Polymer Synthesis, to Fodor, et al., for example, sequential combinations of nucleotides are extended as oligonucleotides growing on a substrate. An array of oligonucleotides having different sequences is prepared by using a system of photoactivation chemistries with reactions directed by illumination of substrate locations through a mask. As with the Agrafiotis technology, reproduction of an array requires reconstruction from scratch by repeating the entire synthesis sequence.
In inorganic materials science, arrays have been prepared using continuous or discrete application of different inorganic materials for reaction on a substrate. For example, in Combinatorial Synthesis of Novel Materials, U.S. Pat. No. 5,985,356, to Shultz, et al., multiple different inorganic materials are applied to multiple regions of an array before reaction of the mixtures to form a combinatorial array of inorganic materials. Shultz, et al., discusses the use of robotics to discretely apply the different materials for combination on the substrate, using masks to direct application of materials to specific regions of a substrate, use of gradients to apply materials to substrates in changing proportions, and spacing array locations to reduce cross contamination. Still, problems remain in providing well defined, homogenous, and repeatable arrays having the same combinations in the same proportions on a substrate. Again, replication of an array in Shultz, et al., requires complete reconstruction of a duplicate array from scratch. This invention can be applied to liquid solution processes for synthesis of a combinatorial array of inorganic materials. However, liquid combinatorial libraries can be difficult to prepare. The general methods of preparation of liquid combinatorial libraries known in the art have problems with stability, homogeneity, and uniformity, especially if the members of the array comprise solvated metal ions. Generally, it is only possible to solvate ions having high valences (e.g., rare earth metal ions such as Ti4+, Ta5+, and Nb5+). Although certain organic solvents may occasionally work in this regard, more often than not the ions precipitate to form non-homogeneous solutions, or an otherwise unstable solution. Even if one is able to produce a solution containing these metal ions, including high valence rare earth metal ions, there is still a potential for precipitation of the ionic species or the instability of the solution if new solvents or reagents are added, or if the solvents from different libraries are combined or mixed. This is especially true for aqueous solutions.
What is needed in the art, therefore, is a way of stabilizing liquid arrays of materials, including solutions of high valence ions, such that the array may be stored for further processing. It is contemplated that such an intermediate array may be commercialized in that stabilized condition, such that another investigator or commercial entity may further process the array according to its own proprietary interests.
The present inventors have developed systems and methods for controlling and maintaining a stable distribution of metal ions in solution at the molecular level, thus ensuring a homogeneous mixture, and these techniques are particularly useful when processing or transferring a liquid master array either to a substrate or to an intermediate liquid array. According to these methods, a metal precursor and a soluble polymer are reacted to form a solution that does not suffer from the conventional problems of gelling or precipitation. The polymer actively binds the metal ion(s) and serves to encapsulate the metal, prevent chemical reactions between constituent ions of the mixture, and maintain the ions in a uniform distribution within the solution. In other words, the polymer functions to ensure a homogeneous metal ion distribution in the solution, and to isolate ions from one another to prevent unwanted reactivity between the metal ion constituents. The stabilized array at this stage could be the master array or a replicate array, and it may comprise an array that exists prior to the final deposition onto a substrate to create the product array. Such stabilized liquid solutions (existing as individual members of an array) may be stable, according to the present embodiments, for up to months at a time.
In view of the above, a need exists for systems and methods to reliably and reproducibly prepare combinatorial arrays of inorganic materials through liquid solutions. It would be desirable to have systems to readily prepare replicate arrays of a homogeneous, well mixed, and stable liquid solution on a practical substrate. The present invention provides these and other features that will be apparent upon review of the following.